Is DOCK2 p.Leu430Val (c.1288C>G) pathogenic?

DOCK2 p.Leu430Val (c.1288C>G) is classified Uncertain significance in DOCK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1041); Very rare (popmax 0.00322%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DOCK2 p.Leu430Val (c.1288C>G)?

DOCK2 p.Leu430Val (c.1288C>G) is associated with Inborn genetic diseases, DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Leu430Val (c.1288C>G) in the general population?

DOCK2 p.Leu430Val (c.1288C>G) is very rare (popmax 0.00322%, nfe) (gnomAD).

What do computational predictors say about DOCK2 p.Leu430Val (c.1288C>G)?

AlphaMissense predicts likely benign (score 0.1041) — an in-silico prediction, not a clinical call.

DOCK2 p.Leu430Val

c.1288C>G · rs370264550 · VCV542615

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1041	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 2.1, phastCons 0.99
Regional constraint	o/e 0.72	unconstrained · MANE · 348 kb · p 3.1e-21 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,890 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00242% 39/1,613,830 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,050
Remaining individualsnot grpmax-eligible	0.0016%	62,476

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DOCK2
Protein: p.Leu430Val
Coding: c.1288C>G
MANE Select: NM_004946
dbSNP: rs370264550
Type: single nucleotide variant
Location: chr5:169702332 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 430: the c2 dock-type domain

Full DOCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: DOCK2 deficiency

Similar variants

DOCK2 c.2267+3G>A Uncertain significance ★★ same condition
DOCK2 c.2704-3C>T Uncertain significance ★★ same condition
DOCK2 c.4467+4A>G Uncertain significance ★★ same condition
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala24Pro Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala454Val Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dock2-p-leu430val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown